Skip to main content
. 2024 Sep 13;27(10):110947. doi: 10.1016/j.isci.2024.110947

Figure 7.

Figure 7

ART initiation in PWH partially normalizes cytokine profiles in CD4+ T cells, with limited impact on CD8+ T cells

(A–F) Univariate analyses of cytokine expression in CD4+ and CD8+ T cells after 15h of aAPCs stimulation of purified T cells from UNT versus ART participants. (A and B) Comparison of total, ORgate-identified, background-subtracted, net cytokine+ (A) CD4+ or (B) CD8+ T cell responses in the UNT and ART cohorts after activation by aAPCs. Both 1:0:4 (aCD3:aCD28:IgG; aCD3 aAPCs, left panel) and 1:4:0 (aCD3:aCD28:IgG; aCD3+aCD28 aAPCs, right panel) stimulations are shown.

(C and D) Comparison of residual signal in the absence of CD28 co-stimulation of total cytokine+ (C) CD4+ or (D) CD8+ T cells between UNT and ART.

(E and F) Comparison of residual signal in the absence of CD28 co-stimulation in CD4+ (E) or CD8+ (F) T cells between UNT and ART for each individual cytokine.

(G–K) Multivariate analyses of cytokine expression in CD4+ and CD8+ T cells after 15h of 1:4:0 (aCD3:aCD28:IgG; aCD3 aCD28 aAPCs) stimulation of purified T cells from UNT versus ART participants, following the same pipeline analyses as in Figures 3 and 6. The CD4+ and CD8+ categorical phenotypic information was reintroduced post-hoc. (G) Multiparametric UMAP representation of cytokine+ CD4+ and CD8+ T cells from ART, based on IL-2, IFNγ, TNFα, CD107a, and IL17A expression after stimulation with aAPCs (aCD3:aCD28:IgG 1:4:0). The colors identify 17 populations clustered by unsupervised analysis using Phenograph. (H and I) Proportions of clusters among cytokine+ (H) CD4+ and (I) CD8+ T cells in UNT vs. ART.

(J and K) Global PCA analysis (on the left) was done with the proportion of clusters in cytokine+ (J) CD4+ or (K) CD8 + activated T cells. The percentage on the x and y axes presents the variance attributed to PC1 and PC2, respectively. On the right, plots of the PC1 and PC2 between groups are shown. In (A–K), UNT n = 13, ART n = 13. Wilcoxon test was used for paired comparisons between UNT and ART. In (A), gray borders represent responses <0.01% that could not be represented on the logarithmic scale and hence were given arbitrary values of 0.01%.